Rx Update: January 2001

Dofetilide

Mary Ross, R.Ph., M.B.A.
Peer Review Status: Internally Reviewed

Dofetilide (Tikosyn® -- Pfizer) is an oral antiarrhythmic agent indicated for the treatment of atrial fibrillation and atrial flutter. Because dofetilide can cause life-threatening ventricular arrhythmias (i.e., torsades de pointes), it should be reserved for patients who are highly symptomatic. Therapy must be initiated in the hospital with continuous cardiac monitoring; the dose is adjusted according to ECG monitoring (QTc interval) and creatinine clearance. Prescribers and the institution are required to sign a form stating that dofetilide will be used in compliance with the Tikosyn® Education Program.

The most common adverse drug reactions with dofetilide are headache, chest pain, and dizziness. Dofetilide should not be used in patients with severe renal impairment (calculated creatinine clearance <20 ml/min) or who have congenital or acquired long QT syndromes. Dofetilide should not be used concomitantly with verapamil, cation transport inhibitors (e.g., cimetidine, trimethoprim, ketoconazole), renal cation transport inhibitors (e.g., prochlorperazine, megestrol), or drugs that prolong the QTc interval (e.g., phenothiazines, cisapride, bepridil, tricyclic antidepressants,, and most macrolides). Dofetilide should also not be used in patients with potassium or magnesium levels outside of the normal range or current conditions that would alter electrolyte balance (e.g., excessive or prolonged diarrhea/vomiting, loss of appetite/thirst, potassium-depleting diuretic).

Before initiating therapy with dofetilide, other Class I or III antiarrhythmic agents should be withheld for at least 3 half-lives prior to starting dofetilide. Upon initiation or re-initiation of dofetilide, the patient must be hospitalized for a minimum of 3 days or a minimum of 12 hours following conversion to normal sinus rhythm, whichever is longer. The recommended dose of dofetilide is 500 mcg twice a day. Dosing ranges from 125 mcg once a day to 500 mcg twice a day after dose adjustments are made for renal function and QT prolongation. Further dosage adjustments should be made two to three hours after the first dose of dofetilide according to QT interval changes. Dofetilide is available as 125 mcg, 250 mcg, and 500 mcg capsules.

Dofetilide prescribing at UIHC is restricted to electrophysiology attending staff physicians who have completed Pfizer's mandated education program. Outpatient prescriptions are only dispensed by one central, mail-order pharmacy that verifies patient and physician completion of the education program.

Valproic Acid Products - Avoid the Confusion

The FDA recently approved a new formulation of valproic acid, De pakote ER®, indicated for the prophylaxis of migraine headaches. Depakote ER® is an extended-release tablet intended to be taken once daily. The recommended dose is 500 to 1000 mg. The original Depakote® tablets are enteric-coated or delayed-release. Enteric-coating helps reduce GI upset by delaying the release of drug until it reaches the intestinal tract, but does not extend the dosing interval. Although both products can be used for migraine headache prophylaxis, they are not bioequivalent, and they cannot be used interchangeably. Outlined below are the available valproic acid preparations.

Brand Name/Strength Formulation Dosing Interval Indication(s)

Depacon® 100 mg/ml

Injection (valproate acid)

8 to 12 hours

Seizures

Depakene® 250 mg/5 ml, 250 mg

Syrup (valproate sodium), Gel capsules (valproic acid)

8 to 12 hours

Seizures

Depakote Sprinkle® 125 mg

Capsule (divalproex sodium)

8 to 12 hours

Seizures

Depakote® 125 mg, 250 mg, 500 mg

Enteric-coated tablet (divalproex sodium)

8 to 12 hours

Seizures, mania, migraine headache prophylaxis

Depakote ER® 500 mg

Extended-release tablet (divalproex sodium)

Once daily

Migraine headache prophylaxis

 

Title Page